Levels of Trace Elements in Erythrocytes as Endocrine Disruptors in Obese and Nonobese Women with Polycystic Ovary Syndrome

Introduction: Polycystic ovary syndrome (PCOS) is one of the most commonly recognized endocrinopathies in women. The literature lacks clear data that allow any meaningful conclusions to be drawn about the influence of trace elements in erythrocytes on the biochemical parameters of PCOS. Materials and methods: This study was conducted among 47 women meeting the Rotterdam criteria for the diagnosis of polycystic ovary syndrome. The research groups included women with PCOS with different BMI values (body mass index): obese women with PCOS (PCOS with BMI ≥ 30, mean BMI index 35.4 ± 4.4 kg/m2), nonobese PCOS women (PCOS with BMI < 30, mean BMI index 25.2 ± 2.8 kg/m2), and healthy control group (CG) with a mean BMI of 23.57 ± 0.9 kg/m2. The contents of trace elements in erythrocytes were determined with an inductively coupled plasma atomic emission spectrometer. Results: The only trace element showing significant differences in concentration between the studied groups was nickel (Ni). The level of nickel in the obese women with PCOS (BMI ≥ 30) was significantly higher than in nonobese women (BMI < 30). The content of other trace elements in erythrocytes did not differ significantly between the studied groups. Several significant correlations were found within each of the studied PCOS groups: in the group of obese women, the content of zinc (Zn) in erythrocytes positively correlated with prolactin, the content of magnesium (Mg) positively correlated with testosterone, and the content of manganese (Mn) negatively correlated with thyroid-stimulating hormone. In the group of nonobese women, Zn content correlated positively with testosterone, Ni with luteinizing hormone (LH) and estradiol, and Mg negatively correlated with estradiol. Conclusions: The relationship between the level of trace elements and the level of hormones suggests that, in obese women with PCOS, nickel may play a role in inhibiting the processes of folliculogenesis and ovulation. Research on trace elements and their relationship to ovulatory cycles and the development of PCOS may contribute to reducing the consequences of PCOS and, therefore, should be extended.

The Independent Association of TSH and Free Triiodothyronine Levels With Lymphocyte Counts Among COVID-19 Patients

BackgroundBoth lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated.MethodsWe included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission.ResultsA total of 541 patients were included. Median LYM was 1.22 x 109/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p&lt;0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p&lt;0.001) and LYM (p&lt;0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend &lt;0.001).ConclusionTSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.

Management of chronic spontaneous urticaria: Real-world Indian perspective

Objectives: There are multiple guidelines for chronic spontaneous urticaria (CSU) by various dermatological associations, but in real-world practice in India, different approaches have been noted. In this paper, we courted to determine these different approaches in CSU management, adherence to various CSU guidelines, and the reasons for deviation from guidelines amidst dermatologists in India. Materials and Methods: A net-based questionnaire was created and validated by five panelists experienced in CSU management and then was circulated to all dermatologists in India in August 2020 for real-world management scenario. Results: We received 880 completed response out of 2235 response. Most of the dermatologists (97%) were aware of some urticaria guidelines. Although many of them follow guidelines about three forth of them reported to deviate from it sometimes. The most common reason for deviation was rely on clinical experience as opted by 53% of respondents. Dermatologists who follow guidelines also investigate routinely in terms of complete blood count, the erythrocyte sedimentation rate, and thyroid-stimulating hormone as compared to those who do not. About 70.5% of the dermatologist prescribe second-generation antihistamine (SGAH) at approved dose as the first line of treatment whereas 63.6% up dose it as second line of treatment. Surprisingly, 68% prescribe first-generation antihistamine in the evening and SGAH in the morning as combination therapy in CSU. Conclusion: From the findings of the present study, it can be strongly implied that guidelines play a vital role in delivering superior attributes of patient care although 75% of dermatologists deviated from it. Main reasons for deviance are reliability on self-clinical proficiency and consideration of economic impediments. Both these factors need to be worked upon by continuous medical education of dermatologists and more pharmaco-economic research.

Mutational screening of the TPO and DUOX2 genes in Argentinian children with congenital hypothyroidism due to thyroid dyshormonogenesis.

Purpose Primary congenital hypothyroidism (CH) is the most common endocrine disease in children and one of the preventable causes of both cognitive and motor deficits. We present a genetic and bioinformatics investigation of rational clinical design in 16 Argentine patients suspected of CH due to thyroid dyshormonogenesis (TDH). Methods Next-Generation Sequencing approach was used to identify variants in Thyroid Peroxidase (TPO) and Dual Oxidase 2 (DUOX2) genes. A custom panel targeting 7 genes associated with TDH [(TPO, Iodothyrosine Deiodinase I (IYD), Solute Carrier Family 26 Member 4 (SLC26A4), Thyroglobulin (TG), (DUOX2), Dual Oxidase Maturation Factor 2 (DUOXA2), Solute Carrier Family 5 Member 5 (SLC5A5)] and 4 associated with thyroid dysembryogenesis [PAX8, FOXE1, NKX2-1, Thyroid Stimulating Hormone Receptor (TSHR)] has been designed. Additionally, bioinformatic analysis and structural modeling were carried out to predict the disease-causing potential variants. Results Five novel variants have been identified, two in TPO: c.2749-2A>C and c.2752_2753delAG, [p.Ser918Cysfs*62] and three variants in DUOX2 gene: c.425C>G [p.Pro142Arg]; c.790delC [p.Leu264Cysfs*57] and c.2695delC [p.Gln899Serfs*21]. Seventeen identified TPO, DUOX2 and IYD variants were previously described. We identified potentially pahogenic bi-allelic variants in TPO and DUOX2 in 8 and 2 patients, respectively. We also detected a potentially pathogenic mono-allelic variant in TPO and DUOX2 in 4 and 1 patients respectively. Only two patients were heterozygous for digenic variants in TPO/IYD and in TPO/DUOX2 genes. Conclusions 22 variants have been identified associated with TDH. All described novel mutations occur in domains important for protein structure and function, predicting the TDH phenotype.

Subacute thyroiditis during early pregnancy: a case report and literature review

Background Subacute thyroiditis (SAT) is rarely diagnosed in pregnant women, and only 7 cases have been reported to date. Thyroid dysfunction, especially hyperthyroidism, during pregnancy has been associated with both maternal and neonatal complications. Thus, the early diagnosis and treatment of SAT during pregnancy may be beneficial. We present a case report and literature review to complement the diagnostic evaluation and management of SAT during pregnancy. Case presentation A 27-year-old woman presented in gestational week 17 of her first pregnancy and had a negative prior medical history. She presented to the Endocrinology Department complaining of neck pain for one month that had intensified in the last five days. Physical examination revealed a diffusely enlarged thyroid gland that was firm and tender on palpation. The patient also had an elevated temperature and heart rate. The increasing and long-lasting pain coupled with a decreased level of thyroid-stimulating hormone indicated hyperthyroidism. Ultrasound findings were indicative of SAT. Importantly, the pain was so severe that 10 mg of oral prednisone per day was administered in gestational week 18, which was increased to 15 mg/d after 10 days that was discontinued in week 28. Levothyroxine was started in gestational week 24 and administered throughout the pregnancy. The patient responded well to the treatments, and her neck pain disappeared in gestational week 21. She gave birth to a healthy male in gestational week 41. Conclusion SAT can be diagnosed and effectively managed during pregnancy, thus benefiting mothers and infants.

Thyroid-stimulating hormone levels in euthyroid patients 8 years following bariatric surgery

Background Bariatric surgery (BS) was shown to promote a decline in thyroid-stimulating hormone (TSH) in euthyroid patients with severe obesity in the short-term. Aim of the present study was to assess the effect of weight loss on thyroid function in euthyroid patients in the long-term following different bariatric procedures. Methods In a retrospective cohort study including 135 patients at baseline, thyroid function was assessed at six time points up to 8 years after surgery. Patients were stratified by TSH levels at baseline and divided into two groups to compare the change in TSH at long-time. We used log-linear regression to assess the relation between thyroid hormones and TSH and linear regression analyses to identify variables that were thought to determine TSH and fT3/fT4-ratio as well as their change long-term. Results Over a mean follow-up of 8 years, TSH and fT3/fT4-ratio declined (both p < 0.001). Patients with high-normal TSH showed a greater decline in TSH than those with normal TSH compared to baseline. Thyroid hormones and TSH displayed a negative log-linear correlation at long-term follow-up. Change in TSH at long-time showed a negative correlation with TSH at baseline (B = −0.55; p < 0.001). With regard to type of surgery, there were no significant differences in TSH. Conclusion BS promotes a decline of TSH in euthyroid patients up to 8 years after intervention despite weight regain. The greatest change in TSH was seen among patients with high-normal baseline-TSH. Results of log-linear regression suggest recovery of the pituitary-thyroid axis. Type of surgery did not affect the change in TSH levels over time.

Indicators of endothelial function and systemic immune inflammatory response in patients with chronic heart failure and coexisting primary hypothyroidism

Chronic heart failure is one of the leading causes of death globally, affecting 1.5 to 2% of the total world population and 2.9 to 3.9% of the total Western European population. Chronic heart failure often progresses rapidly in coexistence with endocrine pathology, namely hypothyroidism, that results in a more rapid development and further progression of endothelial dysfunction and the development of a systemic inflammatory response. The aim of our research was to study the levels of endothelin-1, C-reactive protein, tumor necrosis factor α and their correlation with the levels of thyroid-stimulating hormone, thyroxine in patients with chronic heart failure and coexisting hypothyroidism. There were examined 38 patients with chronic heart failure and coexisting hypothyroidism and 42 patients with chronic heart failure without hypothyroidism. The serum levels of endothelin-1, C-reactive protein, tumor necrosis factor α were determined by the enzyme-linked immunosorbent assay, while the levels of thyroid-stimulating hormone and thyroxine were determined by the electrochemiluminescence immunoassay. In patients with chronic heart failure and coexisting hypothyroidism, the levels of endothelin-1, C-reactive protein, and tumor necrosis factor α were 2.9, 1.5 and 2.27 times higher than those in patients without hypothyroidism. In Group I, there was a moderate positive correlation between the serum levels of endothelin-1 and thyroid-stimulating hormone and a weak negative correlation between the levels of thyroxine and endothelin-1. In Group II, there was a weak correlation between the levels of endothelin-1 and thyroid-stimulating hormone and no correlation between the levels of thyroxine and endothelin-1. In Group I, there was a strong positive correlation between C-reactive protein and thyroid-stimulating hormone levels as well; in Group II, no similar correlation was found. In Group I, there was found a moderate negative correlation between tumor necrosis factor α and thyroxine levels. According to our results, there was a close correlation between the markers of endothelial dysfunction, immune inflammatory response, and single markers of hypothyroidism.

The Association Between COVID-19 and Thyroxine Levels: A Meta-Analysis

ObjectivesRecently, a number of reports have described the potential relationship between COVID-19 and thyroid hormones, but the results were conflicting. We performed a meta-analysis to evaluate the effect of the severity of COVID-19 on thyroid-related hormones and the effect of thyroid-related hormones on the outcome of COVID-19 in order to try to confirm the association between the serum levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) and the severity or mortality of coronavirus-19 patients.MethodsThe methodology was already registered in the International Prospective Register of Systematic Reviews (PROSPERO) database, and the protocol number is CRD42021269246. Systematic searches were carried out on the Cochrane Library, Embase, PubMed and Web of Science databases on November 15, 2021. We set up the literature search strategy based on the following keywords: [(T3 OR FT3 OR triiodothyronine) or (T4 OR FT4 OR thyroxine) or (TSH or thyrotropin)] and (COVID-19 OR SARS-CoV-2), without time restrictions.ResultsTwenty studies satisfied the inclusion/exclusion criteria and were included in the meta-analysis. A total of 3609 patients were enrolled in the study. From the analysis of the included studies, the incidence of thyroid-related hormone abnormalities was higher in patients with severe COVID-19, and the serum levels of FT3 and TSH were lower than those of patients with nonsevere COVID-19. However, the difference in the FT4 levels was not significant. Similar characteristics were shown between survivors and nonsurvivors. In addition, the outcomes of the meta-analysis showed that patients with abnormal thyroid-related hormones had greater mortality.ConclusionsLow FT3 serum levels, low FT4 serum levels and low TSH serum levels may increase the mortality of COVID-19 patients during admission. On the other hand, the higher the severity level of COVID-19, the higher the probability of decreases in the FT3, FT4, TSH levels.

Challenges in the Management of Atrial Fibrillation With Subclinical Hyperthyroidism

Subclinical thyroid disorders have a high prevalence among older individuals and women. Subclinical hypothyroidism is diagnosed by elevated serum levels of thyroid-stimulating hormone (TSH) with thyroxine levels within the reference range, and subclinical hyperthyroidism is diagnosed by low TSH in conjunction with thyroxine and triiodothyronine levels within reference ranges. Atrial fibrillation is the most commonly diagnosed cardiac arrhythmia and has been associated with an increased risk of mortality, heart failure, stroke, and depression. Mechanistic data from animal and human physiology studies as well as observational data in humans support an association of subclinical hyperthyroidism with atrial fibrillation. Guidelines recommend the measurement of TSH in the evaluation of new-onset atrial fibrillation. All patients with overt hyperthyroidism should be treated, and treatment of subclinical hyperthyroidism should be considered in patients older than 65 years with TSH &lt; 0.4 mlU/L, or in younger patients with TSH &lt; 0.1 mlU/L. Guidelines also recommend screening for AF in patients with known hyperthyroidism. Wearable devices that measure the heart electrical activity continuously may be a novel strategy to detect atrial fibrillation in patients at risk. In this review, we explore the interplay between thyroid hormones and atrial fibrillation, management controversies in subclinical hyperthyroidism, and potential strategies to improve the management of atrial fibrillation in patients with subclinical hyperthyroidism.

Initial response of young people with thyrotoxicosis to block and replace or dose titration thionamide

Objective Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy. Methods Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations. Conclusions DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy.